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Table 3 Investigations of structure and function of heart and / or arteries in children and adolescents with JIA with no clinical signs of cardiovascular dysfunction

From: Premature subclinical atherosclerosis in children and young adults with juvenile idiopathic arthritis. A review considering preventive measures

Ref. Design No. of patients and controls Age-group Numbers of patients and subtypes Number of patients in treatment at time of investigation Study parameters Significant findings
Stamato et al. 1995 [78] Descriptive cross-sectional 36 10–17.5 36 HLA-B27 pos. with spondylarthropathy No information Echocardiographic assessment of left ventricle and the outflow tract. Mild aortal regurgitation in patients unrelated to disease duration
with an age matched healthy control group 33 * 6-18 * Atrio-ventricular conduction
Disease duration
Huppertz et al. 2000 [79] Descriptive cross- sectional 40 6–26 35 HLA-B27 pos ERA No information Echocardiographic assessment of the left ventricle functions before and after exercise. HLA-B27 positive ERA possibly at risk for development of aortic regurgitation and impaired myocardial relaxation
with a control group of age and sexmatched HLA-B27 neg JIA and 25 healthy children 15 + 25 * 6 - 25 * 3 oligo Atrio-ventricular conduction  
1 sJIA BP
1 unclassified
Oguz et al. 2000 [80] Descriptive cross- sectional. 30 3–15 19 oligo Mainly NSAID Echocardiographic assessment of the left ventricle function Higher systolic and diastolic BP, but within normal limits, and diastolic dysfunction of abnormal relaxation type in patients
with an age matched healthy control group 30 * 10 poly The patient with systemic JIA received corticosteroid BP
1 sJIA. One unspecified patient received MTX
Argyropoulou et al. 2003 [81] Descriptive cross-sectional 31 No data 18 oligo No information Evaluation by MR of aortic distensibility and PWV Lower distensibility and higher PWV in patients unrelated to JIA subtype
with an age matched healthy control group 28 * 6 poly Disease activity No correlations between aortic distensibility / PWV and metabolic and disease activity parameters
Insulin sensitivity
Lipid profile
7 sJIA
Bharti et al. 2004 [82] Descriptive cross-sectional. 35 No data oligo All received NSAID Eccocardiographic evaluation of left ventricular function Higher systolic and diastolic BP, but within normal rate, and higher resting heart rate in patients.
with an age matched healthy control group 35 * poly Diastolic dysfunction and higher systolic and diastolic dimensions and volumes.
sJIA
No numbers given
Pietrewicz et al. 2007 [83] Descriptive cross-sectional 40 4–16 32 oligo No information Echocardiographic assessment of cIMT Increased cIMT in patients with JIA, highest in children with polyarthritis, and correlation between homocystein and cIMT
Homocysteine
with an age matched control group of healthy children 23 * 3–17 * 8 poly CRP
Lipid profile Correlation between disease duration and cIMT
Disease duration
Vlahos et al. 2011 [84] Descriptive cross-sectional 30 7–18 15 oligo 3 NSAID Echocardiographic assessment of cIMT Reduced FMD in patients (as a group) associated with ESR but without any association to medication or clinical disease activity
with a BMI, sex, and age matched control group of healthy children 33 * 8 poly 4 corticosteroid PWV
FMD
7 sJIA 15 MTX Arterial compliance Increased cIMT in sJIA compared to controls or non-systemic JIA and related to use of corticosteroids, disease activity, BMI, blood pressure, dyslipidaemia, and age
9 TNF-inhibitor Disease activity
BMI
BP
Glucose
Lipid profile No difference in PWV or arterial compliance between groups
Smoking
Koca et al. 2012 [85] Descriptive cross-sectional 50 5–16 22 oligo No information Echocardiographic assessment of left ventricle function Impaired diastolic function in patients
13 poly Electrographic assessment
No arrhythmias
6 ERA
4 PsA
5 sJIA
with a sex, and age matched control group of healthy children 70 *
Follow-up after 12 month.
Abul et al. 2012 [86] Descriptive cross-sectional 55 12.57 SD 2.9 24 oligo 22 NSAID Echocardiographic assessment of right ventricular function Systolic and diastolic dysfunction of the right ventricle
8 poly 31 Salazopyrin
15 ERA 31 MTX
with a BMI, sex, and age matched control group of healthy children 33 * 11.9 SD 2.7 * 1 PsA 25 Corticosteroid Disease activity No association to medication including steroids and no associations to disease activity
7 sJIA 2 TNF-inhibitor
Alkady et al. 2012 [66] Descriptive cross- sectional 45 5–16 5 oligo NSAID Echocardiographic assessment of systolic and diastolic function (36 patients) Higher resting heart rate and higher systolic and diastolic BP in patients but within normal range. Also enlarged left ventricular systolic dimensions and diastolic dysfunction. In 6 patients was found thickened pericardium, and in 9 mitral valve thickening and mild dysfunction.No association with disease activity reported.
10 poly 26 MTX
20 ERA 8 Corticosteroid
with a sex and age matched control group of healthy children 30 * 1 PsA Spirometry and CO diffusion (30 patients)
9 sJIA
23 patients and controls had both investigations
Disease activity and duration
In 19 out of 30 patients was found a reduction in pulmonary function primarily of a restrictive pattern, inversely correlated to disease duration and severity / treatment with MTX
Breda et al. 2012 and 2013 [33, 34] Longitudinal intervention study of 12 months 38 4.7–9.4 Oligo- or poly NSAID cIMT Improvement in all baseline disease parameters, including BT, after one year of “ treatment to target” except cHDL that was found normal at baseline and did not change. Positive correlation between cIMT and LDL and IL-1beta, no correlation to CRP or ESR.
BT was found elevated at baseline but within normal range
Mild disease in 22 MTX at baseline. Clinical disease activity
ESR, CRP
with a sex, age and puberty stage matched control group of healthy children 40 * 4.1- 8.6* Aggressive disease in 16 with poly During follow-up disease control was obtained by 22 in treatment with NSAID +/- conventional DMARDs Proinflammatory cytokines
BP
Lipid profile
Oxidant status
16 patients needed more aggressive treatment with TNF-alfa inhibition
Glowinska-Olszewska et al. 2013 [32] Descriptive cross- sectional 58 11–15 28 oligo 42 Corticosteroid BMI 22% of the patients met the criteria for overweight or obesity.
26 poly 28 MTX FMD
4 sJIA 14 Biologics cIMT
Clin. active inflammation: 30 9 Unspec. DMARDS LVMi Lower FMD and higher cIMT, LVMi, BMI, and BP in patients as a group compared to controls; highest cIMT and lowest FMD in obese patients. No difference between patients with clinically active and inactive disease and no difference between JIA subtypes.
Disease activity
BP
CRP
IL-6, TNF-alfa
Lipid profile
Insulin sensitivity
with a sex and age matched control group of healthy children with normal weight; no obese children 36 * 12-15 * Clin. inactive inflammation: 28
Raab et al. 2013 [36] Descriptive cross- sectional study of young adults with severe JIA, based on self-reports 344 19.7 SD 2.8 28 oligo 215 Biologics Comorbidity In 9.9% were reported CVD with hypertension in 7.3%, not different from the control group
50 extended oligo
91 RFneg poly
37 RFpos poly 151 MTX Disease activity
75 ERA 64 Other conventional Health CVD, mainly hypertension, was reported in 40.6% of 15 patients with sJIA
37 PsA DMARDs Functional deficits,
15 sJIA
11 other arthritis
and compared to an age and sex matched cohort sampled from the general population 688 *  
Aulie et al. 2014 [37] Cross-sectional, observational study of patients with disease duration of more than 23 years 87 34.8–40.6 15 oligo 25 TNF-inhibitor BP Higher systolic and diastolic BT and small elevation of PWV in patients related to diastolic BT
14 extended oligo 19 Methotrexate PWV
13 RF neg poly 23 Daily NSAID AIx
5 RF pos poly 6 Prednisolone Coronary calcification
18 ERA Disease activity No difference in AIx between patients and controls, but a positive association to diastolic BP, accumulated disease parameters inclusive treatment with prednisolone, and daily smoking, and a negative association to vigorous physical activity
15 PsA
CRP, ESR
BMI and waist circumference
4 sJIA Lipid profile
3 unclassified Insulin resistance
Self reported habits of smoking and physical activity
With an age and sex matched group without DM or inflammatory arthritis selected from a national population register 87 *
Coronary calcification was present in 26% of patients, a frequency not different from that found in a large population study, and related to waist circumference, BMI, systolic BP, blood glucose and years on daily prednisolone
Lianza et al. 2014 [77] Two year prospective observational study 21 2.2–17.8 21 poly TNF-inhibitor Systolic and diastolic cardiac function evaluated by echocardiography Mild ventricular diastolic dysfunction in JIA with no relation to NT-pro-BNP. Possible association between NT-pro-BNP and disease activity.
  with age and sex matched healthy controls 22 * 6 - 17 * Cardiac biomarkers: NT-pro-BNP
Troponin T No sign of cardiovascular deterioration during treatment with TNF-alfa inhibitor.
Disease activity
Satija et al. 2014 [71] Cross sectional, observational 31 3.5–16 2 oligo No DMARD or biologics cIMT, Reduced arterial elasticity in patients indicative of increased stiffness, all had normal BT. No difference in cIMT, FMD, GTN-MD between subgroups and controls
2 RF neg poly Arterial elasticity
FMD
31 *
GTN-MD
BT
4 RF pos poly Disease activity
9 ERA ESR
14 sJIA Lipid-profile Correlation between cIMT and ESR
With an age and sex matched control group of healthy children
  1. SD is given in brackets. Aix Augmentation index, aIMT aorta intima-media thickness, BP blood pressure, CAC, coronary artery calcification, cIMT, carotis intima-media thickness, ERA Entesitis-related arthritis, ESR erythrocyte sedimentation rate, FMD flow mediated dilatation, GTN-MD glyceryl trinitrate mediated dilatation, LVMi left ventricle mass index, MTX Methotrexate, NSAID Non Steroid Anti-Inflammatory Drug, Oligo oligoarticular JIA, RF Rheuma-factor, Poly Polyarticular JIA, PsA Psoriasis associated JIA, sJIA systemic JIA, DMARD disease modifying anti-rheumatic drugs, PWV pulse wave velocity